You'd Prefer An Argonaute

2011 Keystone RNAi meeting. Enhhh.

Posted in Conferences by YPAA on April 15, 2011

I didn’t go to this meeting, but it sounded like there were fewer marquee talks this year, due in part to the host of other small RNA meetings recently. Plus it was raining cats and dogs in Monterey. Thus the “Enhhh.”

Still a few nuggets worth mentioning though.

Ian MacRae told an interesting result of guide strands being unloaded more with increased complementarity, especially in the 3′ end, to the target RNA. Introducing more mismatches could inhibit unloading. Therefore when targets are present, miRNAs are more stable in AGO than siRNAs, possibly due to the acrobatics that AGO performs to accomodate a ~19-21mer duplex, especially the PAZ domain which interacts with the 3′ end of the guide. I imagine the degree of this effect is also AGO specific.

The structure of C3PO, an endoribonuclease that promotes RISC activation by removing siRNA passenger strand cleavage products, was solved twice and was compared to an avocado and the Death Star. Yay.                          

There was a bit of controversy regarding a paper published by Rachel Green’s group early last year which proposed an allosteric site in the MID domain that could bind the 5′ cap of mRNAs (which I presented in RNA Journal Club and reviewed here). Filipp Frank from Nahum Sonenberg’s group presented convincing biochemical and structural studies that showed no functional evidence for this allosteric site in the MID domain.

Argument over the mechanism of miRNA repression–mRNA degradation vs. translational repression in both temporal and absolute senses continued to be hotly debated.

Elisa Izaurralde pushed the idea that deadenylation is a direct effect of miRNA action, and not solely a consequence of translational repression.

One of the most intriguing talks came from Antonio Giraldez. His lab has been doing ribosome profiling in zebrafish during early embryogenesis where miR-430 dominates to clear maternal mRNAs, so the system is pretty clean. His main point was that in this scenario, at one time point where miR-430 expression peaks, there is translational repression without mRNA degradation. At the next time point a couple hours later, mRNA degradation comes into play, perhaps even slightly more than translational repression. Understanding the kinetics of deadenylation in relation to mRNA degradation will be key to interpreting these data from time points so close to miR-430 expression peaking.

Lastly, lush biochemistry is still the essence of the Yuki Tomari lab. They have some nice in vitro assays to follow piRNA processing, namely trimming of precursor molecules by a yet unidentified nuclease whose function seems to be coupled with methylation of the piRNAs.

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